Cues associated with drug reward acquire particular significance in motivating drug-related behavior. Investigating the neural basis of cue-reward learning is therefore important to understanding addictive states, in which the frequent consumption of abusive drugs "hijacks" natural reward systems. A novel form of reward-related plasticity was recently observed in the primary visual cortex (V1) of adult rats trained to associate visual stimulation with water reward: neurons that previously reported only the physical attributes of the stimulus began to also indicate the time of expected reward. The goals of the proposed research are 1) to investigate the underlying neural mechanism leading to reward-time learning in V1 and 2) to determine if this reward-timing activity is relevant to guiding the animal's reward-seeking behavior. The Specific Aims seek to demonstrate that a neuromodulatory reward signal, in combination with visual stimulation, is both necessary and sufficient to lead to the formation of reward-timing activity in V1. Specific Aim 1 is to BLOCK the reward signal, hypothesized to be acetylcholine acting on muscarinic receptors, during the operant conditioning task previously used to induce reward-timing activity in V1. By locally infusing a muscarinic antagonist during training, it is expected that the formation of reward-timing activity, as measured by multi-unit extracellular recording, will be impaired. The effect on behavior will be assessed by comparing the responses on unrewarded catch trials from normally trained and blockade trained animals. Specific Aim 2 is to MIMIC the reward signal by pairing visual stimulation with local photolytic uncaging of a muscarinic agonist. If muscarinic receptor activation is sufficient to induce reward-timing activity, neurons will begin to report the uncaging time associated with visual stimulation. Further, by altering previously established reward-timing activity with uncaging, it is hypothesized that the animal's response on unrewarded trials will shift from the time of reward to the time of uncaging. PUBLIC HEALTH RELEVANCE: The proposed research contributes to our understanding of how the brain assigns meaning to cues in the environment and produces appropriate behavior. This knowledge is highly important to the study of learning and decision-making, both under normal circumstances and in maladaptive states such as drug addiction.